Primary Research Articles Research Articles

Atypical Signs and Symptoms of Giant Cell Arteritis: A Systematic Review.

Giant cell arteritis can present with atypical manifestations that delay treatment and risk severe complications. To comprehensively describe all atypical signs/symptoms of giant cell arteritis. In this systematic review, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to October 2022. Primary research articles that included at least one participant with an atypical sign/symptom of biopsy-proven giant cell arteritis were included. Study screening and data extraction were performed in duplicate. The primary outcome was the proportion of participants with atypical giant cell arteritis features. Time to treatment was compared between participants with atypical giant features only and participants with both typical and atypical features. Of 21,828 screened records, 429 studies corresponding to 746 individuals (median [IQR] age 72 [IQR, 66-78] years, 63% female) with at least one atypical feature of GCA were included. Eighty-two percent had both atypical and at least one concurrent typical giant cell arteritis feature, whereas 18% of patients with atypical signs and symptoms only presented with atypical features. Patients with atypical symptoms presented to clinicians earlier than patients with typical features (p < 0.001). There was no difference between groups in proportion to elevated ESR and CRP (82.3% vs. 83.35%, p = 0.91) or mortality rate (8.2% vs. 10.8%, p = 0.42). Patients with atypical features only experienced greater delay in treatment initiation (p < 0.001). The most commonly reported atypical signs/symptoms were vertigo (11.9%), scalp necrosis/ulceration (7.9%), and dry cough (5.8%). Eighteen percent of biopsy-proven giant cell arteritis cases with at least one atypical feature have only atypical features and are more likely to experience delays in treatment. Clinicians should be aware of atypical signs/symptoms of giant cell arteritis and order inflammatory markers early to prevent giant cell arteritis-associated morbidity.

The effect of outdoor air pollution on Alzheimer’s disease: a systematic review

Abstract Air pollution is one of the largest global environmental risks to public health. Over recent years, neuroimaging techniques have started to uncover the detrimental impact air pollution has had on brain health, including the development of Alzheimer’s Diseases (AD). We systematically reviewed the literature to evaluate the effects of long-term exposure (months to years) to outdoor air pollutants on the development of AD-like neurology. This review was registered on PROSPERO (CRD42023482979) and followed PRISMA guidelines. Four large databases (MEDLINE, Embase, Scopus, and CINAHL) were searched in November 2023 using terms associated with air pollution, neuroimaging, and AD. Only peer-reviewed primary research articles using neuroimaging data to examine AD-like pathology after long-term exposure to air pollutants (Particulate Matter (PM2.5, PM10), SO2, NO2, O3, and/or CO) were included. Titles, abstracts and full-texts were screened, and included articles were quality assessed using the Newcastle Ottawa Scale. A narrative synthesis was conducted to analyse the studies. Our search yielded 397 results, of which eight articles met our inclusion criteria. Articles focused on changes to white matter (n = 5), cortical thickness (n = 6), and grey matter (n = 2). Exposure to PM2.5 was commonly associated with white matter reductions, and PM10 and NO2 exposure was associated with reduced cortical thickness. The effect of exposure to different outdoor pollution on grey matter was inconclusive, with both increases and decreases in grey matter volume observed. This review highlighted how PM2.5, PM10 and NO2 exposure was associated with neurological changes commonly seen in AD. These findings can be used by policymakers and researchers to identify specific pollutants that need greater restrictions and regulations to improve population health. Key messages • PM2.5, PM10 and NO2 exposure are associated with neurological changes commonly seen in AD. • Greater restrictions and regulations are needed on specific pollutants to improve population health.

Stereotactic Radiosurgery for Intracranial Breast Metastases: A Systematic Review and Meta-Analysis

Background/Objectives: To determine the impact of stereotactic radiosurgery on outcomes of metastatic breast cancer with intracranial metastases. Methods: We systematically searched the PubMed and EMBASE databases for studies published between 1 January 1990 and 1 August 2024. Primary research articles evaluating the outcomes of stereotactic radiosurgery on intracranial metastases from breast cancer were included. Adverse events were defined as leptomeningeal disease, radiation necrosis, seizure, and headache. The pooled estimate was calculated using the DerSimonian and Laird approach. Results: Sixteen studies encompassing 1228 patients met the inclusion criteria. Our analysis revealed a median survival duration of 13.1 ± 3.8 months and a pooled 1-year overall survival rate of 53.1% after SRS treatment. There was a 29% local recurrence rate at 1 year and a 35% overall distant recurrence rate. In addition, our analysis found a relatively low rate of acute adverse events at 15.5%. Conclusions: SRS demonstrates promising efficacy and safety in managing intracranial metastases from breast cancer, with a favorable toxicity profile.

Mouse Models of HER2+ Human Breast Cancer: A Literature Review

Introduction: HER2+ breast cancer (BC) makes up 15-20% of BC cases, where HER2 overexpression drives BC progression via proliferative signals. Targeted therapies inhibit HER2's activity but face challenges like resistance and metastasis. Thus, HER2+ BC is a developing research area where many preclinical studies are being conducted, and mice are often used due to their genetic and physiological similarities to humans. This study aims to review and compare existing mouse models to determine the best model of HER2+ BC. Methods: A literature search on PubMed in February 2024 using search terms including HER2, neu, neuNT, MMTV, and mammary tumors identified 16 primary research articles that used Neu-overexpressing mice. The papers were categorized under five models: MMTV-Neu, MMTV-NeuNT, FloxNeo-NeuNT, MMTV-NIC, and MMTV-HER2. Results: Among examined studies, Andrechek et al.'s FloxNeo-NeuNT model had the longest average tumor onset at 447 days, while Kuang et al.'s MMTV-NIC had the shortest at 126 days. Ursini-Segal et al.'s MMTV-NIC mice showed 100% mammary tumor incidence. Most models resulted in mammary adenocarcinomas, with lung metastases commonly observed, especially in papers that used MMTV-NIC. Discussion: Human HER2+ BC is commonly adenocarcinoma and often metastasizes to lungs, bones, liver, and brain. The mouse models were also found to be adenocarcinomas, but they primarily showed lung metastasis, possibly due to insufficient tumor detection methods for brain and bone metastasis. Neu copy numbers in Andrechek et al.’s FloxNeo-NeuNT model also align with findings on HER2 copy number amplification in human HER2+ BC. Conclusion: We have found that MMTV-NIC is the optimal mouse model for HER2+ BC research due to its short latency, 100% tumor incidence, and high rate of lung metastasis.

Weight-control compensatory behaviors patterns and correlates: a scoping review.

Weight-control compensatory behaviors appear to be a commonly utilized strategy for health management. Individuals engaging in such behaviors believe that the negative consequences from unhealthy behaviors will be neutralized by the positive consequences of healthy behaviors. Existing research has not reached a consensus on whether such behaviors are beneficial to health. This review aims to (1) summarize the patterns of weight-control compensatory health behaviors in different populations, (2) highlight correlates, predictors, and consequences of compensatory health behaviors, and (3) identify gaps for future research. This review identified existing literature using online databases, CINAHL and PubMed. Primary research articles published after 2000 with non-clinical participants of 12 years or older who engaged in compensatory behaviors for weight control purposes were selected. Descriptive statistics were extracted from 35 studies. Different patterns for weight-control compensatory behaviors emerged between the female and male sexes. Meanwhile, no clear association of such behaviors was found across weight status. Studies reviewed also highlighted three main areas of compensatory behaviors for weight management, namely dietary behaviors, physical activity, and alcohol consumption. Weight-control compensatory behaviors had significant negative correlations with mental health indicators, such as psychosocial functioning, emotional differentiation ability, and body esteem. Weight-control compensatory behaviors may be a widely used weight management strategy and can be presented in diverse ways. Although believed to be promoting health, such behaviors appear to be associated with poor psychological well-being. This emerging topic warrants more in-depth investigation to establish the direction of causation. Future research may investigate the relationship between weight-control compensatory behaviors and various aspects of health over longer time periods, examine the engagement of multiple weight-control compensatory behaviors, and focus on high-risk populations.

Technology Trends and Augmented Reality: A Systematics Literature Review

The real environment is combined with artificial virtual things to create a dynamic, context-based and interactive augmented reality. Therefore, with the latest advances in augmented reality technology and using diverse displays in mobile computing system, augmented reality is affordable for the public. However, its use, as well as the variety of concepts have not yet been fully explored. Therefore, on this page, we describe the variety of industries that have used augmented reality in a variety of uses as well as a variety of displays. Therefore, in order to find relevant data about various industries using augmented reality, a review study involving filtering information from two databases was done. The results of the analysis found a total of 2,929 primary research articles that had been published between 2020 and 2024. While the literature review found that the authors paid attention to the sample size, methodology, devices used, field and results. We conclude that augmented reality design technology is able to thrive by incorporating more fields and capabilities.

How to conduct an integrative mixed methods meta-analysis: A tutorial for the systematic review of quantitative and qualitative evidence.

This article is a guide on how to conduct mixed methods meta-analyses (sometimes called mixed methods systematic reviews, integrative meta-analyses, or integrative meta-syntheses), using an integrative approach. These aggregative methods allow researchers to synthesize qualitative and quantitative findings from a research literature in order to benefit from the strengths of both forms of analysis. The article articulates distinctions in how qualitative and quantitative methodologies work with variation to develop a coherent theoretical basis for their integration. In advancing this methodological approach to integrative mixed methods meta-analysis (IMMMA), I provide rationales for procedural decisions that support methodological integrity and address prior misconceptions that may explain why these methods have not been as commonly used as might be expected. Features of questions and subject matters that lead them to be amenable to this research approach are considered. The steps to conducting an IMMMA then are described, with illustrative examples, and in a manner open to the use of a range of qualitative and quantitative meta-analytic approaches. These steps include the development of research aims, the selection of primary research articles, the generation of units for analysis, and the development of themes and findings. The tutorial provides guidance on how to develop IMMMA findings that have methodological integrity and are based upon the appreciation of the distinctive approaches to modeling variation in quantitative and qualitative methodologies. The article concludes with guidance for report writing and developing principles for practice. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Literature Review: The Effectiveness of Eye Movement Desensitization and Reprocessing Therapy for Race-Based Traumatic Stress With African Americans

Background:Race-based traumatic stress is defined as psychological and emotional stress induced by race-based offenses in the life span. Examples of this include but are not limited to overt verbal and physical racist encounters, microaggressions, housing discrimination, racist policies, racist policing practices, employment discrimination, and economic disenfranchisement. African Americans are disproportionately affected, and it is not clear if mental health treatment is effective.Objective:The purpose of the study was to examine the effects of race-based traumatic stress on African Americans and examine if eye movement desensitization and reprocessing (EMDR) therapy is an effective treatment modality. The author sought to answer the following question: If African Americans who have been exposed to race-based traumatic stress receive EMDR therapy, will it reduce emotional and psychological distress associated with race-based trauma?Methods:A literature review was conducted between January 22 and April 26 of 2024. The following online databases contributed to the selection of peer-reviewed articles for this literature review: APA PsycArticles, APA PsycInfo, CINAHL Complete, and Educational Resources Information Center. Gray literature such as the National Alliance on Mental Illness’s database was also explored to locate additional statistics and information concerning mental health, race-based traumatic stress, and African Americans. Reference lists of the identified articles were manually reviewed, and additional relevant articles such as primary research articles were included in the literature review.Findings:It could not be concluded that EMDR therapy is an effective modality for treating race-based traumatic stress in African Americans. Thus, the answer appears to be unclear currently.Conclusions:The findings suggest that further research and advocacy are necessary to better understand the effectiveness of specialized modalities and mental health care concerning treatment for African Americans.

Exhaustive Search of Dietary Intake Biomarkers as Objective Tools for Personalized Nutrimetabolomics and Precision Nutrition Implementation.

To conduct an exhaustive scoping search of existing literature, incorporating diverse bibliographic sources to elucidate the relationships between metabolite biomarkers in human fluids and dietary intake. The search for biomarkers linked to specific dietary food intake holds immense significance for precision health and nutrition research. Using objective methods to track food consumption through metabolites offers a more accurate way to provide dietary advice and prescriptions on healthy dietary patterns by healthcare professionals. An extensive investigation was conducted on biomarkers associated with the consumption of several food groups and consumption patterns. Evidence is integrated from observational studies, systematic reviews, and meta-analyses to achieve precision nutrition and metabolism personalization. Tailored search strategies were applied across databases and gray literature, yielding 158 primary research articles that met strict inclusion criteria. The collected data underwent rigorous analysis using STATA and Python tools. Biomarker-food associations were categorized into 5 groups: cereals and grains, dairy products, protein-rich foods, plant-based foods, and a miscellaneous group. Specific cutoff points (≥3 or ≥4 bibliographic appearances) were established to identify reliable biomarkers indicative of dietary consumption. Key metabolites in plasma, serum, and urine revealed intake from different food groups. For cereals and grains, 3-(3,5-dihydroxyphenyl) propanoic acid glucuronide and 3,5-dihydroxybenzoic acid were significant. Omega-3 fatty acids and specific amino acids showcased dairy and protein foods consumption. Nuts and seafood were linked to hypaphorine and trimethylamine N-oxide. The miscellaneous group featured compounds like theobromine, 7-methylxanthine, caffeine, quinic acid, paraxanthine, and theophylline associated with coffee intake. Data collected from this research demonstrate potential for incorporating precision nutrition into clinical settings and nutritional advice based on accurate estimation of food intake. By customizing dietary recommendations based on individualized metabolic profiles, this approach could significantly improve personalized food consumption health prescriptions and support integrating multiple nutritional data.This article is part of a Nutrition Reviews special collection on Precision Nutrition.

Online active learning in undergraduate dental education: A scoping review.

Research on online active learning (OAL) in dental education has increased in recent years; however, this literature has yet to be comprehensively summarized to document the available evidence and identify research gaps. This scoping review aimed to comprehensively map the extent and depth of the research activity on OAL in undergraduate dental education. The review adhered to Arksey & O'Malley's multi-step framework and followed the PRISMA Extension Scoping Reviews guidelines. Searches were conducted in MEDLINE, Embase, Scopus, and ERIC databases for peer-reviewed primary research articles in English published between December 2013 and 2023. Four trained researchers independently screened titles, abstracts, and full-text articles for eligibility and extracted relevant data. All activities and information were cross-checked by the same researchers. A tested, methodologically-informed form was used for data extraction. Descriptive statistics and content analysis were used to summarize the extracted data. Thirty-five articles were included in the review. Most studies focused on dental students exclusively, with only two studies involving students and faculty. All studies performed outcome evaluations at reaction and/or learning levels. Problem-based learning, case-based learning, small group discussion, flipped learning, and blended learning were the most common active learning strategies employed. Dental students were satisfied with OAL and perceived it as beneficial for knowledge acquisition and skill development. Test results confirmed the improvement of knowledge through OAL. OAL has shown to improve learning outcomes in dental education; however, robust research designs are needed to further demonstrate its effectiveness in this educational context.

Women Veterans' Stroke Risk Factors: Identified Prevention Methods and Knowledge Gaps.

Stroke is a significant health burden for veterans and the fifth leading cause of death for women. Compared to civilian women, women veterans have significant multimorbid physical and mental health conditions contributing to their stroke risk. This scoping review aimed to synthesize evidence on the stroke risk factors specific to U.S. women veterans and identify any association between risk factors and a delay in prevention and treatment for women veterans. This study was approved by the organizational Institutional Review Board. The search strategy was run across 6 databases: MEDLINE and EMBASE via Ovid, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. A total of 1218 records were uploaded to Covidence for screening. Criteria for included studies were peer-reviewed primary research articles written in English about women veterans and cardiovascular disease and stroke risk factors. No restrictions were placed on publication date. Fourteen articles met the inclusion criteria. Cohorts were 30 years and older. Data originated from national and individual Veterans Affairs studies. Women veterans starting at age 30 have a steadily increasing positive curvilinear association with stroke risk, indicating a need to screen earlier than the recommended age of 45 years. Stroke incidence was higher in veterans with post-traumatic stress disorder, insomnia, restless leg syndrome, traumatic brain injury, constipation with laxative use, egg consumption (2-4 eggs/wk), frailty, and systemic sclerosis. When comparing White veterans and civilian counterparts, Black veterans had a higher incidence of stroke. Ten studies addressed prevention methods. The clinicians should screen and treat women veterans for post-traumatic stress disorder and constipation and consider alternative treatment methods for constipation. Empirical literature on this matter is lacking. Examining and understanding the differences in sex, gender, and veteran status, and their association with stroke risk, is warranted. Screening women veterans for post-traumatic stress disorder and for stroke early, at 30 years of age, is recommended.

Advancing Oncology through Imaging: Evaluating FDG-PET's Role in Cancer Diagnosis and Staging

Purpose: Fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) represents a valuable functional molecular imaging technique. Through non-invasive means, 18F-FDG PET allows for the assessment of glucose metabolic activity in living biological systems. Its utility in oncology is well established, with applications in tumor diagnosis, staging, and treatment monitoring. The purpose of this study is to conduct a systematic review assessing the indicative value and effect on the clinical management of 18F-FDG PET/CT for various cancer types based on the current literature. Materials and Methods: An inclusive search of the PubMed, Google Scholar, and Science Direct databases was performed to identify relevant studies published from 2022 to the present. Records were screened according to predefined inclusion and exclusion criteria. A full-text review of the eligible studies was independently conducted by two reviewers. Results: Twenty-one primary research articles met the inclusion criteria and encompassed several cancer types. Evidence demonstrates superior detection, characterization, and staging compared with anatomical imaging alone. Advantages have been substantiated for head/neck, lung, and brain cancers, as well as lymphomas. The significant associations between 18F-FDG uptake and clinical features validated the molecular profiling capacity. Conclusion: 18F-FDG PET provides crucial metabolic tumor information, augmenting conventional approaches. Specific diagnostic values have been established for diverse oncological applications. While technical refinements are ongoing, 18F-FDG PET plays an expanding role in multimodal cancer algorithms according to guidelines. Continued investigation aims to further optimize these techniques and clarify their comparative effectiveness.

Impact of organic foods on chronic diseases and health perception: a systematic review of the evidence.

The aim of the present systematic review was to evaluate the existing data on the health impacts, of the consumption of organically grown foods versus conventionally farmed alternatives, with specific focus on the postulated health superiority of organic foods. A systematic literature research was performed in PubMed, Embase, Web of Science, and Google Scholar. Inclusion criteria were articles on adults (>18 years of age) consuming organic foods for ≥6 months, written in English language, and provision of comparative results between conventional and organic nutrition regarding health indices. From 1760 identified references, 21 primary research articles (2006-2022) met the inclusion criteria. Outcomes related to chronic disease prevalence, biomarker effects, and exposure to pesticides and other harmful substances were evaluated. A significant inverse relationship between organic food consumption and cardiometabolic risk factors, including obesity, diabetes mellitus, hypertension, and hyperlipidemia, was observed in the majority of prospective studies. The data on cancer risk and nutrient value comparison between organic and conventional foods were inconclusive. Clinical trials consistently indicated lower pesticide exposure in participants on organic diets, suggesting potential health benefits. The consumption of organic foods is associated with reduced cardiometabolic risks and pesticide exposure. However, the long-term impact on cancer risk remains undetermined. Future long-term studies are needed to establish whether an organic diet is superior to a conventional one in terms of overall health benefits.

Ultrasound-stimulated microbubbles to enhance radiotherapy: A scoping review.

Primarily used as ultrasound contrast agents, microbubbles have recently emerged as a versatile therapeutic vector that can be 'burst' to deliver payloads in the presence of suitably optimised ultrasound fields. Ultrasound-stimulated microbubbles (USMB) have recently demonstrated improvements in treatment outcomes across a variety of clinical applications. This scoping review investigates whether this potential translates into the context of radiation therapy by evaluating the application of this technology across all three phases of radiation action. Primary research articles, excluding poster presentations and conference proceedings, were identified through systematic searches of the PubMed NCBI/Medline, Embase/OVID, Web of Science and CINAHL/EBSCOhost databases, with additional articles identified via manual Google Scholar searching. Articles were dual screened for inclusion using the Covidence systematic review platform and classified against all three phases of radiation action. Overall, 57 eligible publications from a total of 1389 identified articles were included in the review, with studies dating back to 2012. Study heterogeneity prevented formal statistical analysis; however, most articles reported improved outcomes using USMB in the presence of radiation compared to that of radiation alone. These improvements appear to result from the use of USMB as either a biovascular disruptor causing tumour cell damage via indirect mechanisms, or as a localised treatment vector that directly increases tumour cell uptake of other therapeutic and physical agents designed to enhance radiation action. USMB demonstrate exciting potential to enhance the effects of radiation treatments due to their versatility and capacity to targetall three phases of radiation action.

Understanding metastatic involvement of the conus medullaris: a systematic review of clinical presentations, diagnostic approaches, treatment options, and patient outcomes.

Metastasis to the conus medullaris (CM) is a rare but devastating condition. This systematic review aimed to evaluate the clinical presentation, diagnostic workup, treatment options, and outcomes of patients with CM metastasis. By synthesizing the available evidence, this study seeks to improve our understanding of this condition and inform clinical practice. A systematic review adhering to PRISMA guidelines analyzed literature on CM metastasis from 1997 to January 2024. Human studies in English were included, focusing on primary research articles. Screening criteria ensured a homogeneous study population, with data analyzed using SPSS 26 and assessed for quality using the JBI checklist. The study analyzed 88 patients with conus medullaris metastasis. Common symptoms included back pain (49.3%), sensory impairment (75%), and bladder dysfunction (60.3%). MRI was the primary diagnostic tool, revealing lesions above L1 (37%) or between L1 and L2 (29%). Treatment involved surgery with laminectomy, and combined therapy (surgery plus radiotherapy) in 81.3%. Postoperative outcomes showed improved motor function in 59.6% of patients, while combined therapy yielded better sensory and bowel/bladder function recovery. Median survival was 100 days. Metastasis to the conus medullaris is rare but significant. Surgical resection can improve motor function, while combined therapy (surgery plus radiotherapy) is effective in improving sensory manifestations and bowel/bladder functions. Despite these treatments, the median survival remains around 100 days, which is shorter compared to other types of intramedullary spinal cord metastases.

Glenohumeral capsular injury rate in patients with glenohumeral instability: a systematic review and meta-analysis

Glenohumeral instability is a complex clinical problem with underlying pathology in the bony, labral, and capsular tissues. The rate of specific capsular injuries varies widely in the literature and the clinical importance of these specific injury patterns remains unclear. Following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines, a systematic review was performed of multiple databases for all primary research articles between 2008 and 2023 which included advanced imaging and included rates of capsular injury in patients with glenohumeral instability. Twelve studies met inclusion criteria. The most prevalent capsular injury seen was in the inferior glenohumeral ligament (34.1%) across all studies, followed by anterior labroligamentous periosteal sleeve avulsions with 24.9% prevalence. Humeral avulsions of the glenohumeral ligaments lesions were the least common (6.2%) of subjects, followed closely by capsular tears (8.3%) of subjects. Capsular injury is commonly seen in magnetic resonance imaging of patients with anterior shoulder instability. Significant heterogeneity in language and imaging techniques was found in the existing literature. Further research is needed to explore these specific capsular lesions' clinical implications and rehabilitation strategies.

Is physical activity an effective remedy for insomnia? - a review

Introduction and purpose This article explores the impact of physical activity on insomnia and sleep quality. It reviews existing research to clarify how exercise affects sleep patterns, identifies mechanisms through which exercise improves sleep, and evaluates practical recommendations for integrating physical activity into insomnia treatment. The goal is to offer valuable insights for individuals and healthcare professionals on using exercise as a non-pharmacological method to manage insomnia. State of knowledge The article reviews the literature on sleep, with a particular focus on the issue of insomnia. By understanding the causes of sleep disorders, it is possible to implement targeted diagnostics and subsequent treatment. The impact of physical activity on the overall problem of insomnia is also highlighted. Material and Methods A review of literature from 2004 to 2024 was conducted using databases such as PubMed, Science Direct, and Google Scholar. Keywords included "insomnia," "sleep disorder," and "sleep impairment." The review focused on English-language primary research articles from peer-reviewed journals. Summary The review highlights the role of physical activity in managing insomnia, emphasizing its positive effects. Evidence indicates that regular exercise significantly reduces the risk and severity of insomnia and improves sleep quality. This underscores the effectiveness of physical activity as a valuable non-pharmacological approach to enhancing sleep and overall well-being. Keywords Insomnia; physical activity; sleep disorders; quality of sleep; sport

Timing of SMN replacement therapies in mouse models of spinal muscular atrophy: a systematic review and meta-analysis.

Mutations in the Survival of Motor Neuron 1 gene lead to a loss of survival motor neuron protein in patients with spinal muscular atrophy. Revolutionary advances in gene therapy have led to survival motor neuron-replacement therapies that significantly prolong life expectancy and improve neuromuscular function. However, accumulating evidence suggests that the timing of survival motor neuron-replacement therapies is a critical determinant of success. We performed a systematic review and meta-analysis of all pre-clinical studies testing survival motor neuron replacement therapies in mouse models of spinal muscular atrophy to assess the impact of timing of delivery on therapeutic effectiveness. We incorporated four databases in this pre-registered study (PROSPERO 2020 CRD42020200180): EMBASE, PubMed, Scopus and Web of Science. Inclusion criteria were; primary research article, a measure of survival analysis, use of survival motor neuron mouse model and evaluation of survival motor neuron-targeting therapy. Exclusion criteria included; use of therapies not known to directly target survival motor neuron, genetic manipulations and/or lack of appropriate controls. We screened papers using the SyRF platform. The main outcome we assessed was survival in treated groups compared to untreated groups. We performed meta-analysis of survival using median survival ratio and the random effects model and measured heterogeneity using the I 2 statistic. Subgroup analyses were performed to assess treatment efficacy based on timing of intervention (embryonic delivery, day of birth, postnatal day 2 and postnatal day 3 or later) and treatment type. If detailed in the studies, body weight compared to untreated spinal muscular atrophy models and motor neuron number were included as secondary outcomes for meta-analysis. 3469 studies were initially identified, with 78 ultimately included. Survival motor neuron-replacement therapies significantly affected survival in favour of treatment by a factor of 1.20 (95% CI 1.10-1.30, P < 0.001) with high heterogeneity (I 2 = 95%). Timing of treatment was a significant source of heterogeneity (P < 0.01), with earlier treatment having a greater impact on survival. When stratified by type of treatment, earlier treatment continued to have the strongest effect with viral vector replacement therapy and antisense oligonucleotide therapy. Secondary outcome measures of body weight and spinal motor neuron counts were also positively associated with early treatment. Earlier delivery of survival motor neuron replacement therapies is therefore a key determinant of treatment efficacy in spinal muscular atrophy.

Teaching Scientific Literature Analysis: A Systematic Adoption of Skill-Building Methods to Enrich Research Training for Undergraduate Students.

Teaching scientific literature analysis skills is a critical step in research training. Here I describe a 6-week skill-building module on understanding scientific literature, incorporated into a 10-week undergraduate honors research practice course in Neuroscience. Key pedagogical components include: 1) student-centered active-learning, skill-building and community-building activities; 2) persistent adoption of a proven CREATE method and a novel curate scientific summary (CSS) method for teaching scientific literature analysis skills; 3) collaborative class organization consisting of persistent learning pods (PLPs) to facilitate student-driven participation and peer learning; and, 4) role play of a real research lab. Skill development was assessed using a self-assessment survey (SAS) and longitudinal evaluation of the CREATE and CSS methods application by the PLPs to analyze primary research articles (PRAs) over four weeks. Outcomes demonstrate alleviation of pre-existing student anxiety to read complex scientific literature and advancement of critical-thinking and collaborative skills. Specifically, the SAS responses indicate that student perception about reading scientific literature transformed from being a daunting task to an enjoyable activity; this enhanced their confidence in evaluating scientific literature. PLPs fostered student engagement, peer instruction, and community building, and contributed to skill development. Weekly assessment of CREATE and CSS application highlighted marked improvements in students' abilities to analyze and critique complicated scientific material. Role playing a research lab setting with a focused research theme facilitated integrative understanding of a frontier topic in Neuroscience. The outlined innovative approach can be adopted in Course-based Undergraduate Research Experience (CURE) and should help contribute to systematizing didactic practices to train neuroscientists.

Mapping simulation-based activities for health professionals in rural and remote contexts in high-income countries: a scoping review protocol.

This scoping review will aim to map the existing academic literature on simulation-based activities that are designed with and delivered for health professionals in geographically rural and remote contexts in high-income countries. Simulation-based health care activities are implemented in health services to increase patient safety because they allow health professionals to prepare, learn, practice, rehearse, and improve clinical performance and teamwork. Simulation-based activities are increasingly being used in rural and remote areas, where resources are limited compared with metropolitan areas. This review will include all primary and peer-reviewed research articles and abstracts that report health simulation methodologies and activities that have been used in rural and remote health care contexts in high-income countries. The proposed review will follow the JBI guidelines for scoping reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) guidelines. Databases to be searched will include Embase, Emcare, and MEDLINE (all searched via Ovid), Scopus, PubMed, and the Cochrane Database. Titles and abstracts will be screened independently by 2 reviewers, followed by full-text screening. Data will be extracted and analyzed to address the review questions. Open Science Framework https://osf.io/pu6gv.